There is significant evidence for the role that CD8 [unreadable] CTL play in the containment of HIV and SIV, particularly during the acute phase of infection. However, increasingly it is becoming evident that one of the major factors limiting the success of these responses lies within the propensity of HIV and SIV to mutate and escape from these responses. While the more powerful techniques are now allowing for the comprehensive analysis and mapping CD8 responses to HIV, a similar analysis of viral diversity and escape is still lacking. A few studies have examined viral escape within some defined HIV CD8 epitopes. However, a comprehensive analysis of is still lacking. Furthermore, the elimination of wild-type virus by certain CD8 responses during acute infection implies effective containment of viral replication by these responses. In support of this, many acute escaping responses in SIV have been found to exhibit high functional avidity, a characteristic of CD8 responses associated with the effective control of other viral infections. These findings suggest that such CD8 responses may represent very potent responses. Identifying similar responses in HIV may help to define better immunogens and vaccine targets against HIV. In addition, it will be important to begin investigating the impact that viral diversity between different HIV-1 strains has on cross- recognition of CD8 responses. Understanding the role that CD8 responses play in controlling viral replication in the setting of a potential HIV-1 superinfection provides an opportunity to study this. By comparing comprehensive CD8 cellular responses with whole genome viral sequencing of two viruses differentially emerging over time we may be able to determine the impact that HIV-1 diversity has on the ability of a pre-existing CD8 response to control HIV-I. The proposed project, therefore, will use whole viral genome sequencing along with cellular assays to examine these issues.